Displaying publications 21 - 40 of 54 in total

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  1. Divis PCS, Duffy CW, Kadir KA, Singh B, Conway DJ
    Mol Ecol, 2018 02;27(4):860-870.
    PMID: 29292549 DOI: 10.1111/mec.14477
    Plasmodium knowlesi is a significant cause of human malaria transmitted as a zoonosis from macaque reservoir hosts in South-East Asia. Microsatellite genotyping has indicated that human infections in Malaysian Borneo are an admixture of two highly divergent sympatric parasite subpopulations that are, respectively, associated with long-tailed macaques (Cluster 1) and pig-tailed macaques (Cluster 2). Whole-genome sequences of clinical isolates subsequently confirmed the separate clusters, although fewer of the less common Cluster 2 type were sequenced. Here, to analyse population structure and genomic divergence in subpopulation samples of comparable depth, genome sequences were generated from 21 new clinical infections identified as Cluster 2 by microsatellite analysis, yielding a cumulative sample size for this subpopulation similar to that for Cluster 1. Profound heterogeneity in the level of intercluster divergence was distributed across the genome, with long contiguous chromosomal blocks having high or low divergence. Different mitochondrial genome clades were associated with the two major subpopulations, but limited exchange of haplotypes from one to the other was evident, as was also the case for the maternally inherited apicoplast genome. These findings indicate deep divergence of the two sympatric P. knowlesi subpopulations, with introgression likely to have occurred recently. There is no evidence yet of specific adaptation at any introgressed locus, but the recombinant mosaic types offer enhanced diversity on which selection may operate in a currently changing landscape and human environment. Loci responsible for maintaining genetic isolation of the sympatric subpopulations need to be identified in the chromosomal regions showing fixed differences.
  2. Fernando HA, Chandramouli C, Rosli D, Lam YL, Yong ST, Yaw HP, et al.
    Nutrients, 2014 Nov 04;6(11):4856-71.
    PMID: 25375630 DOI: 10.3390/nu6114856
    Glycyrrhizic acid (GA) ameliorates many components of the metabolic syndrome, but its potential therapeutic use is marred by edema caused by inhibition of renal 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2). We assessed whether 100 mg/kg per day GA administered orally could promote metabolic benefits without causing edema in rats fed on a high-sucrose diet. Groups of eight male rats were fed on one of three diets for 28 days: normal diet, a high-sucrose diet, or a high-sucrose diet supplemented with GA. Rats were then culled and renal 11β-HSD2 activity, as well as serum sodium, potassium, angiotensin II and leptin levels were determined. Histological analyses were performed to assess changes in adipocyte size in visceral and subcutaneous depots, as well as hepatic and renal tissue morphology. This dosing paradigm of GA attenuated the increases in serum leptin levels and visceral, but not subcutaneous adipocyte size caused by the high-sucrose diet. Although GA decreased renal 11β-HSD2 activity, it did not affect serum electrolyte or angiotensin II levels, indicating no onset of edema. Furthermore, there were no apparent morphological changes in the liver or kidney, indicating no toxicity. In conclusion, it is possible to reap metabolic benefits of GA without edema using the current dosage and treatment time.
  3. Mohamed M, Lim SC, Mumtaz M, Uppal S, Mukherjee D, Kassim MSM, et al.
    J ASEAN Fed Endocr Soc, 2023;38(1):37-44.
    PMID: 37252419 DOI: 10.15605/jafes.038.01.12
    OBJECTIVES: Insulin degludec (IDeg)/insulin aspart (IAsp; IDegAsp) is a co-formulation of 70% IDeg and 30% IAsp. According to several randomized controlled trials, IDegAsp is effective and safe for patients with type 2 diabetes mellitus (T2DM). A subgroup analysis of the ARISE study was conducted to explore the safety and efficacy of IDegAsp among Malaysian patients with T2DM in real-world settings.

    METHODOLOGY: ARISE, an open-label, multicenter, non-interventional, prospective study was conducted between August 2019 and December 2020. Adult Malaysian patients with T2DM who were enrolled from 14 sites received IDegAsp as per the local label for 26 weeks. The primary endpoint was change in glycated hemoglobin (HbA1c) levels from baseline to end of study (EOS).

    RESULTS: Of the 182 patients included in the full analysis set, 159 (87.4%) completed the study. From baseline to EOS, HbA1c (estimated difference [ED]: -1.3% [95% CI: -1.61 to -0.90]) and fasting plasma glucose levels (ED: -1.8 mmol/L [95% CI: -2.49 to -1.13]) were significantly reduced (p<0.0001). The patient-reported reduced hypoglycemic episodes (overall and nocturnal) during treatment. Overall, 37 adverse events were observed in 23 (12.6%) patients.

    CONCLUSION: Switching or initiating IDegAsp treatment resulted in significant improvements in glycemic control and a reduction in hypoglycemic episodes.

  4. Yaw HP, Ton SH, Amanda S, Kong IG, Cheng HS, Fernando HA, et al.
    PMID: 25755839
    Stress and high-calorie diet increase the risk of developing metabolic syndrome. Glycyrrhizic acid (GA) has been shown to improve hyperglycaemia and dyslipidaemia under various physiological conditions. This study was aimed at examining the effects of stress and GA on glucose metabolism under short- or long-term stress. Forty-eight Sprague Dawley rats were divided into two groups with constant stress induced by light (300-400 lux) for either 14 days (short-term stress) or 28 days (long-term stress). Within each group, the rats were subdivided into three treatment groups i.e. Group A (control group): high-calorie diet (HCD) only; Group B: HCD + stress (14 or 28 days) and Group C: HCD + stress (14 or 28 days) + GA (100 mg/kg). The blood glucose concentrations of the rats exposed to 14-day stress were elevated significantly and GA lowered blood glucose concentration significantly in the 14-day exposure group. The 28-day exposure group adapted to stress as shown by the lower adrenaline level and gluconeogenic enzymes activities in most of the tissues than the 14-day exposure group. With regards to adrenaline and corticosterone, GA was found to increased adrenaline significantly in the short-term exposure group while lowering corticosterone in the long-term exposure group. GA-treated short- and long-term exposure groups had significant reduction in hexose-6-phosphate dehydrogenase activities in the visceral adipose tissues and quadriceps femoris respectively. The results may indicate the role of GA in improving blood glucose concentration in individuals exposed to short-term stress who are already on a high-calorie diet via selective action on gluconeogenic enzymes in different tissues.
  5. Lim WY, Chia YY, Liong SY, Ton SH, Kadir KA, Husain SN
    Lipids Health Dis, 2009;8:31.
    PMID: 19638239 DOI: 10.1186/1476-511X-8-31
    The metabolic syndrome (MetS) is a cluster of metabolic abnormalities comprising visceral obesity, dyslipidaemia and insulin resistance (IR). With the onset of IR, the expression of lipoprotein lipase (LPL), a key regulator of lipoprotein metabolism, is reduced. Increased activation of glucocorticoid receptors results in MetS symptoms and is thus speculated to have a role in the pathophysiology of the MetS. Glycyrrhizic acid (GA), the bioactive constituent of licorice roots (Glycyrrhiza glabra) inhibits 11beta-hydroxysteroid dehydrogenase type 1 that catalyzes the activation of glucocorticoids. Thus, oral administration of GA is postulated to ameliorate the MetS.
  6. Fong CY, Hlaing CS, Tay CG, Abdul Kadir KA, Goh KJ, Ong LC
    Eur. J. Paediatr. Neurol., 2016 May;20(3):449-53.
    PMID: 26900103 DOI: 10.1016/j.ejpn.2016.01.012
    Longitudinal extensive transverse myelitis associated with dengue infection is rare with no reported paediatric cases.
  7. Fungfuang W, Udom C, Tongthainan D, Kadir KA, Singh B
    Malar J, 2020 Oct 01;19(1):350.
    PMID: 33004070 DOI: 10.1186/s12936-020-03424-0
    BACKGROUND: Certain species of macaques are natural hosts of Plasmodium knowlesi and Plasmodium cynomolgi, which can both cause malaria in humans, and Plasmodium inui, which can be experimentally transmitted to humans. A significant number of zoonotic malaria cases have been reported in humans throughout Southeast Asia, including Thailand. There have been only two studies undertaken in Thailand to identify malaria parasites in non-human primates in 6 provinces. The objective of this study was to determine the prevalence of P. knowlesi, P. cynomolgi, P. inui, Plasmodium coatneyi and Plasmodium fieldi in non-human primates from 4 new locations in Thailand.

    METHODS: A total of 93 blood samples from Macaca fascicularis, Macaca leonina and Macaca arctoides were collected from four locations in Thailand: 32 were captive M. fascicularis from Chachoengsao Province (CHA), 4 were wild M. fascicularis from Ranong Province (RAN), 32 were wild M. arctoides from Prachuap Kiri Khan Province (PRA), and 25 were wild M. leonina from Nakornratchasima Province (NAK). DNA was extracted from these samples and analysed by nested PCR assays to detect Plasmodium, and subsequently to detect P. knowlesi, P. coatneyi, P. cynomolgi, P. inui and P. fieldi.

    RESULTS: Twenty-seven of the 93 (29%) samples were Plasmodium-positive by nested PCR assays. Among wild macaques, all 4 M. fascicularis at RAN were infected with malaria parasites followed by 50% of 32 M. arctoides at PRA and 20% of 25 M. leonina at NAK. Only 2 (6.3%) of the 32 captive M. fascicularis at CHA were malaria-positive. All 5 species of Plasmodium were detected and 16 (59.3%) of the 27 macaques had single infections, 9 had double and 2 had triple infections. The composition of Plasmodium species in macaques at each sampling site was different. Macaca arctoides from PRA were infected with P. knowlesi, P. coatneyi, P. cynomolgi, P. inui and P. fieldi.

    CONCLUSIONS: The prevalence and species of Plasmodium varied among the wild and captive macaques, and between macaques at 4 sampling sites in Thailand. Macaca arctoides is a new natural host for P. knowlesi, P. inui, P. coatneyi and P. fieldi.

  8. Wong YQ, Tan LK, Seow P, Tan MP, Abd Kadir KA, Vijayananthan A, et al.
    PLoS One, 2017;12(6):e0179895.
    PMID: 28658309 DOI: 10.1371/journal.pone.0179895
    OBJECTIVES: This study assesses the whole brain microstructural integrity of white matter tracts (WMT) among older individuals with a history of falls compared to non-fallers.

    METHODS: 85 participants (43 fallers, 42 non-fallers) were evaluated with conventional MRI and diffusion tensor imaging (DTI) sequences of the brain. DTI metrics were obtained from selected WMT using tract-based spatial statistics (TBSS) method. This was followed by binary logistic regression to investigate the clinical variables that could act as confounding elements on the outcomes. The TBSS analysis was then repeated, but this time including all significant predictor variables from the regression analysis as TBSS covariates.

    RESULTS: The mean diffusivity (MD) and axial diffusivity (AD) and to a lesser extent radial diffusivity (RD) values of the projection fibers and commissural bundles were significantly different in fallers (p < 0.05) compared to non-fallers. However, the final logistic regression model obtained showed that only functional reach, white matter lesion volume, hypertension and orthostatic hypotension demonstrated statistical significant differences between fallers and non-fallers. No significant differences were found in the DTI metrics when taking into account age and the four variables as covariates in the repeated analysis.

    CONCLUSION: This DTI study of 85 subjects, do not support DTI metrics as a singular factor that contributes independently to the fall outcomes. Other clinical and imaging factors have to be taken into account.

  9. Yaw HP, Ton SH, Chin HF, Karim MK, Fernando HA, Kadir KA
    PMID: 26069530
    Stress and high-calorie diets increase the risk of developing metabolic syndrome. Glycyrrhizic acid (GA) has been shown to improve dyslipidaemia in rats fed on a high-calorie diet. This study aimed to examine the effects of GA on lipid metabolism in rats exposed to short- or long-term stress and on a high-calorie diet. The parameters examined included serum lipid profiles, serum free fatty acids and fatty acid profiles in tissues, and expression of peroxisome proliferator-activated receptors (PPAR), lipoprotein lipase (LPL), elongases and desaturases. Within the 14- or 28-day exposure groups, neither stress nor GA affected the lipid profile and serum free fatty acids. Stress did not affect PPAR-α expression in both the 14- and 28-day exposure groups. However, GA-treated rats from the former group had increased PPAR-α expression only in the kidney while all other tissues from the latter group were unaffected. Stress increased PPAR-γ expression in the heart of the 28-day exposure group but its expression was unaffected in all tissues of the 14-day exposure group. GA elevated PPAR-γ expression in the kidney and the skeletal muscles. Neither stress nor GA affected LPL expressions in all tissues from the 14-day exposure group but its expressions were elevated in the QF of the stressed rats and heart of the GA-treated rats of the 28-day exposure group. As for the elongases and desaturases in the liver, stress down-regulated ELOVL5 in the long-term exposure group while up-regulated ELOVL6 in the short-term exposure group while hepatic desaturases were unaffected by stress. Neither elongase nor desaturase expressions in the liver were affected by GA. This research is the first report of GA on lipid metabolism under stress and high-calorie diet conditions and the results gives evidence for the role of GA in ameliorating MetS via site-specific regulation of lipid metabolism gene expressions and modification of fatty acids.
  10. Kyaw TZ, Maniam JA, Bee PC, Chin EF, Nadarajan VS, Shanmugam H, et al.
    Turk J Haematol, 2012 Sep;29(3):278-82.
    PMID: 24744674 DOI: 10.5505/tjh.2012.94809
    Acute promyelocytic leukemia with concurrent myeloid sarcoma is a rare clinical event. Herein we describe a patient that presented with back pain and bilateral leg weakness caused by spinal cord compression due to extramedullary deposition of leukemic cells. Acute promyelocytic leukemia was suspected based on immunophenotypic findings of malignant cells in bone marrow aspirate. The diagnosis was confirmed by the presence of PML-RARα fusion copies. MRI showed multiple hyperintense changes on the vertebral bodies, together with intraspinal masses causing spinal cord compression. The patient immediately underwent radiotherapy, and was treated with all-trans retinoic acid and idarubicin. Reassessment MRI showed complete resolution of all intraspinal masses and the disappearance of most of the bony lesions. Post-treatment bone marrow aspirate showed complete hematological and molecular remission. The motor power of his legs fully recovered from 0/5 to 5/5; however, sensory loss below the T4 level persisted.
  11. Yap NJ, Hossain H, Nada-Raja T, Ngui R, Muslim A, Hoh BP, et al.
    Emerg Infect Dis, 2021 08;27(8):2187-2191.
    PMID: 34287122 DOI: 10.3201/eid2708.204502
    We detected the simian malaria parasites Plasmodium knowlesi, P. cynomolgi, P. inui, P. coatneyi, P. inui-like, and P. simiovale among forest fringe-living indigenous communities from various locations in Malaysia. Our findings underscore the importance of using molecular tools to identify newly emergent malaria parasites in humans.
  12. Raja TN, Hu TH, Kadir KA, Mohamad DSA, Rosli N, Wong LL, et al.
    Emerg Infect Dis, 2020 08;26(8):1801-1809.
    PMID: 32687020 DOI: 10.3201/eid2608.200343
    To monitor the incidence of Plasmodium knowlesi infections and determine whether other simian malaria parasites are being transmitted to humans, we examined 1,047 blood samples from patients with malaria at Kapit Hospital in Kapit, Malaysia, during June 24, 2013-December 31, 2017. Using nested PCR assays, we found 845 (80.6%) patients had either P. knowlesi monoinfection (n = 815) or co-infection with other Plasmodium species (n = 30). We noted the annual number of these zoonotic infections increased greatly in 2017 (n = 284). We identified 6 patients, 17-65 years of age, with P. cynomolgi and P. knowlesi co-infections, confirmed by phylogenetic analyses of the Plasmodium cytochrome c oxidase subunit 1 gene sequences. P. knowlesi continues to be a public health concern in the Kapit Division of Sarawak, Malaysian Borneo. In addition, another simian malaria parasite, P. cynomolgi, also is an emerging cause of malaria in humans.
  13. Ang JXD, Kadir KA, Mohamad DSA, Matusop A, Divis PCS, Yaman K, et al.
    Parasit Vectors, 2020 Sep 15;13(1):472.
    PMID: 32933567 DOI: 10.1186/s13071-020-04345-2
    BACKGROUND: Plasmodium knowlesi is a significant cause of human malaria in Sarawak, Malaysian Borneo. Only one study has been previously undertaken in Sarawak to identify vectors of P. knowlesi, where Anopheles latens was incriminated as the vector in Kapit, central Sarawak. A study was therefore undertaken to identify malaria vectors in a different location in Sarawak.

    METHODS: Mosquitoes found landing on humans and resting on leaves over a 5-day period at two sites in the Lawas District of northern Sarawak were collected and identified. DNA samples extracted from salivary glands of Anopheles mosquitoes were subjected to nested PCR malaria-detection assays. The small subunit ribosomal RNA (SSU rRNA) gene of Plasmodium was sequenced, and the internal transcribed spacer 2 (ITS2) and mitochondrial cytochrome c oxidase subunit 1 (cox1) gene of the mosquitoes were sequenced from the Plasmodium-positive samples for phylogenetic analysis.

    RESULTS: Totals of 65 anophelines and 127 culicines were collected. By PCR, 6 An. balabacensis and 5 An. donaldi were found to have single P. knowlesi infections while 3 other An. balabacensis had either single, double or triple infections with P. inui, P. fieldi, P. cynomolgi and P. knowlesi. Phylogenetic analysis of the Plasmodium SSU rRNA gene confirmed 3 An. donaldi and 3 An. balabacensis with single P. knowlesi infections, while 3 other An. balabacensis had two or more Plasmodium species of P. inui, P. knowlesi, P. cynomolgi and some species of Plasmodium that could not be conclusively identified. Phylogenies inferred from the ITS2 and/or cox1 sequences of An. balabacensis and An. donaldi indicate that they are genetically indistinguishable from An. balabacensis and An. donaldi, respectively, found in Sabah, Malaysian Borneo.

    CONCLUSIONS: Previously An. latens was identified as the vector for P. knowlesi in Kapit, central Sarawak, Malaysian Borneo, and now An. balabacensis and An. donaldi have been incriminated as vectors for zoonotic malaria in Lawas, northern Sarawak.

  14. De Ang JX, Yaman K, Kadir KA, Matusop A, Singh B
    Sci Rep, 2021 Apr 08;11(1):7739.
    PMID: 33833272 DOI: 10.1038/s41598-021-86107-3
    Plasmodium knowlesi is the main cause of malaria in Sarawak, where studies on vectors of P. knowlesi have been conducted in only two districts. Anopheles balabacensis and An. donaldi were incriminated as vectors in Lawas and An. latens in Kapit. We studied a third location in Sarawak, Betong, where of 2169 mosquitoes collected over 36 days using human-landing catches, 169 (7.8%) were Anopheles spp. PCR and phylogenetic analyses identified P. knowlesi and/or P. cynomolgi, P. fieldi, P. inui, P. coatneyi and possibly novel Plasmodium spp. in salivary glands of An. latens and An. introlatus from the Leucosphyrus Group and in An. collessi and An. roperi from the Umbrosus Group. Phylogenetic analyses of cytochrome oxidase subunit I sequences indicated three P. knowlesi-positive An. introlatus had been misidentified morphologically as An. latens, while An. collessi and An. roperi could not be delineated using the region sequenced. Almost all vectors from the Leucosphyrus Group were biting after 1800 h but those belonging to the Umbrosus Group were also biting between 0700 and 1100 h. Our study incriminated new vectors of knowlesi malaria in Sarawak and underscores the importance of including entomological studies during the daytime to obtain a comprehensive understanding of the transmission dynamics of malaria.
  15. Tai ML, Nor HM, Kadir KA, Viswanathan S, Rahmat K, Zain NR, et al.
    Medicine (Baltimore), 2016 Jan;95(1):e1997.
    PMID: 26735523 DOI: 10.1097/MD.0000000000001997
    Paradoxical manifestation is worsening of pre-existing tuberculous lesion or appearance of new lesions in patients whose condition initially improved with antituberculous treatment. Our hypothesis was that paradoxical manifestation in non-HIV tuberculous meningitis (TBM) patients was underestimated and this could contribute to patients' prognosis. This was the first systemic study of paradoxical manifestation in HIV-negative TBM patients. Between 2009 and 2014, TBM patients were studied prospectively in 2 hospitals. Clinical features, cerebrospinal fluid, and radiological findings were monitored. Paradoxical manifestation was divided into definite (4 weeks or more) and probable (between 14 and 27 d) after commencement of antituberculous treatment. Forty-one non-HIV TBM patients were recruited. Definite paradoxical manifestation occurred in 23/41 (56%) of the patients. Time to onset of paradoxical manifestation was between 28 days and 9 months, and majority was between 28 and 50 days. Neuroimaging manifestation in the brain (22/41 patients, 54%) and clinical manifestation (22/41 patients, 54%) were most commonly seen, followed by cerebrospinal fluid manifestation (7/41 patients, 17%). Neuroimaging changes most commonly seen were worsening of leptomeningeal enhancement, new infarcts, new tuberculomas, and enlargement of tuberculoma. Initial Computed Tomography Angiography/magnetic resonance angiography brain showed vasculitis in 14 patients, with 2 (12.5%) showing paradoxical vasculitis during follow-up. Recurrence of the paradoxical manifestation was seen in 7/23 (30%) of the patients. More than half (14/23, 61%) of the patients improved, 6 (26%) patients died, and 3 (13%) patients had persistent neurological deficit. Paradoxical manifestation was very common in non-HIV TBM patients. Neuroimaging paradoxical manifestation of 2-4 weeks may not be paradoxical manifestation but could be delayed treatment response.
  16. Gamalo LE, Dimalibot J, Kadir KA, Singh B, Paller VG
    Malar J, 2019 Apr 24;18(1):147.
    PMID: 31014342 DOI: 10.1186/s12936-019-2780-4
    BACKGROUND: Macaca fascicularis (long-tailed macaque) is the most widespread species of macaque in Southeast Asia and the only species of monkey found naturally in the Philippines. The species is the natural host for the zoonotic malaria species, Plasmodium knowlesi and Plasmodium cynomolgi and for the potentially zoonotic species, Plasmodium inui. Moreover, other Plasmodium species such as Plasmodium coatneyi and Plasmodium fieldi are also natural parasites of M. fascicularis. The aims of this study were to identify and determine the prevalence of Plasmodium species infecting wild and captive long-tailed macaques from the Philippines.

    METHODS: A total of 95 blood samples from long-tailed macaques in the Philippines were collected from three locations; 30 were from captive macaques at the National Wildlife Rescue and Rehabilitation Center (NWRRC) in Luzon, 25 were from captive macaques at the Palawan Wildlife Rescue and Conservation Center (PWRCC) in Palawan and 40 were from wild macaques from Puerto Princesa Subterranean River National Park (PPSRNP) in Palawan. The Plasmodium spp. infecting the macaques were identified using nested PCR assays on DNA extracted from these blood samples.

    RESULTS: All 40 of the wild macaques from PPSRNP in Palawan and 5 of 25 captive macaques from PWRCC in Palawan were Plasmodium-positive; while none of the 30 captive macaques from the NWRRC in Luzon had any malaria parasites. Overall, P. inui was the most prevalent malaria parasite (44.2%), followed by P. fieldi (41.1%), P. cynomolgi (23.2%), P. coatneyi (21.1%), and P. knowlesi (19%). Mixed species infections were also observed in 39 of the 45 Plasmodium-positive macaques. There was a significant difference in the prevalence of P. knowlesi among the troops of wild macaques from PPSRNP.

    CONCLUSION: Wild long-tailed macaques from the island of Palawan, the Philippines are infected with P. knowlesi, P. inui, P. coatneyi, P. fieldi and P. cynomolgi. The prevalence of these Plasmodium spp. varied among the sites of collection and among troops of wild macaques at one site. The presence of these simian Plasmodium parasites, especially P. knowlesi and P. cynomolgi in the long-tailed macaques in Palawan presents risks for zoonotic transmission in the area.

  17. Hocking SE, Divis PCS, Kadir KA, Singh B, Conway DJ
    Emerg Infect Dis, 2020 08;26(8):1749-1758.
    PMID: 32687018 DOI: 10.3201/eid2608.190864
    Most malaria in Malaysia is caused by Plasmodium knowlesi parasites through zoonotic infection from macaque reservoir hosts. We obtained genome sequences from 28 clinical infections in Peninsular Malaysia to clarify the emerging parasite population structure and test for evidence of recent adaptation. The parasites all belonged to a major genetic population of P. knowlesi (cluster 3) with high genomewide divergence from populations occurring in Borneo (clusters 1 and 2). We also observed unexpected local genetic subdivision; most parasites belonged to 2 subpopulations sharing a high level of diversity except at particular genomic regions, the largest being a region of chromosome 12, which showed evidence of recent directional selection. Surprisingly, we observed a third subpopulation comprising P. knowlesi infections that were almost identical to each other throughout much of the genome, indicating separately maintained transmission and recent genetic isolation. Each subpopulation could evolve and present a broader health challenge in Asia.
  18. Assefa S, Lim C, Preston MD, Duffy CW, Nair MB, Adroub SA, et al.
    Proc Natl Acad Sci U S A, 2015 Oct 20;112(42):13027-32.
    PMID: 26438871 DOI: 10.1073/pnas.1509534112
    Malaria cases caused by the zoonotic parasite Plasmodium knowlesi are being increasingly reported throughout Southeast Asia and in travelers returning from the region. To test for evidence of signatures of selection or unusual population structure in this parasite, we surveyed genome sequence diversity in 48 clinical isolates recently sampled from Malaysian Borneo and in five lines maintained in laboratory rhesus macaques after isolation in the 1960s from Peninsular Malaysia and the Philippines. Overall genomewide nucleotide diversity (π = 6.03 × 10(-3)) was much higher than has been seen in worldwide samples of either of the major endemic malaria parasite species Plasmodium falciparum and Plasmodium vivax. A remarkable substructure is revealed within P. knowlesi, consisting of two major sympatric clusters of the clinical isolates and a third cluster comprising the laboratory isolates. There was deep differentiation between the two clusters of clinical isolates [mean genomewide fixation index (FST) = 0.21, with 9,293 SNPs having fixed differences of FST = 1.0]. This differentiation showed marked heterogeneity across the genome, with mean FST values of different chromosomes ranging from 0.08 to 0.34 and with further significant variation across regions within several chromosomes. Analysis of the largest cluster (cluster 1, 38 isolates) indicated long-term population growth, with negatively skewed allele frequency distributions (genomewide average Tajima's D = -1.35). Against this background there was evidence of balancing selection on particular genes, including the circumsporozoite protein (csp) gene, which had the top Tajima's D value (1.57), and scans of haplotype homozygosity implicate several genomic regions as being under recent positive selection.
  19. Mustafa N, Kamarudin NA, Ismail AA, Khir AS, Ismail IS, Musa KI, et al.
    Diabetes Care, 2011 Jun;34(6):1362-4.
    PMID: 21498788 DOI: 10.2337/dc11-0005
    OBJECTIVE:
    To determine the prevalence of prediabetes and diabetes among rural and urban Malaysians.
    RESEARCH DESIGN AND METHODS:
    This cross-sectional survey was conducted among 3,879 Malaysian adults (1,335 men and 2,544 women). All subjects underwent the 75-g oral glucose tolerance test (OGTT).
    RESULTS:
    The overall prevalence of prediabetes was 22.1% (30.2% in men and 69.8% in women). Isolated impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) were found in 3.4 and 16.1% of the study population, respectively, whereas 2.6% of the subjects had both IFG and IGT. Based on an OGTT, the prevalence of newly diagnosed type 2 diabetes was 12.6% (31.0% in men and 69.0% in women). The prediabetic subjects also had an increased prevalence of cardiovascular disease risk factors.
    CONCLUSIONS:
    The large proportion of undiagnosed cases of prediabetes and diabetes reflects the lack of public awareness of the disease.
  20. Mohamud WN, Ismail Aa, Khir AS, Ismail IS, Musa KI, Kadir KA, et al.
    Diabetes Res Clin Pract, 2012 04;96(1):91-7.
    PMID: 22553777 DOI: 10.1016/j.diabres.2011.11.020
    Aim: To report the national prevalence of metabolic syndrome (MetS) and its risk factors among adult Malaysians (>18 years old) based on World Health Organization (WHO), the National Cholesterol Education Program Expert Panel III (ATP III), International Diabetes Federation (IDF) and the 'Harmonized' criteria.Methods: A multi-stage stratified sampling method was used to select 4341 subjects from Peninsular and East Malaysia. Subjects underwent physical and clinical examinations.Results: Based on the WHO, ATP III, IDF and Harmonized definitions, the overall crude prevalences of MetS were 32.1, 34.3, 37.1 and 42.5%, respectively. Regardless of the criteria used, MetS was higher in urban areas, in females, in the Indian population and increased significantly with age. Risk factors also increased with age; abdominal obesity was most prevalent (57.4%), was higher in females (64.2%) and was highest in Indians (68.8%).Hypertension was higher in males (56.5%) and highest among Malays (52.2%). In contrast,the Chinese had the highest prevalence of hypertriglyceridemia (47.4%).Conclusions: Malaysia has a much higher prevalence of MetS compared with other Asian countries and, unless there is immediate intervention to reduce risk factors, this may pose serious implications on the country's healthcare costs and services.
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